When to order an ANA:

Useful / Not Useful
Suspected Diseases / SLE
Drug induced lupus
Scleroderma
Dermato-/Polymyositis
Sjogren’s
MCTD / Rheumatoid Arthritis
Psoriatic Arthritis
Enteropathic Arthritis
Ankylosing Spondylitis
Giant Cell Arteritis
Polymyalgia Rheumatica
Vasculitis
Behcet’s disease
Clinical presentation
(typically requires ≥2) / Arthritis
Rash*
Myositis†
Oral ulcers
Alopecia
Dry eyes/ dry mouth
Sclerodactyly
Raynaud’s
Pleuritis/Pericarditis
Intersitial lung disease
Hemolytic anemia
Leukopenia
Thrombocytopenia
Urinary RBC casts
Glomerulonephritis
Proteinuria / Systemic inflammatory signs alone, such as fever of unknown origin
Back pain
  • Positive ANA tests do not need to be repeated.
  • Negative ANA tests may be repeated to re-evaluate diagnoses if the clinical picture changes.

*For example, photosensitive, malar, discoid, Gottron’s, heliotrope, Shawl’s, mechanic’s hands, purpura, ulcers, livedo reticularis.

Proportion of healthy adults with +ANA1:

1:40 / 31.7%
1:80 / 13.3%
1:160 / 5%
1:320 / 3.3%

Female sex and increasing age tend to be more commonly associated with positive ANA.

Causes of positive ANA not associated with rheumatic diseases

(Usually weak titre, <1:160)

  • Viral infections
  • Thyroid disease
  • Liver disease
  • Malignancies
  • Medications

Sensitivity of ANA for Connective Tissue Diseases2

Sensitivity
SLE / 97.41*
Scleroderma / 85%
Dermato-/Polymyositis / 61%
Sjogren’s Syndrome / 48%
Secondary Raynaud’s / NA†

* Applies to ANA test using indirect immunofluorescence with Hep-2 cells.

† Up to 19% of patients with Raynaud’s will have a connective tissue disease.

Positive ANA increases proportion to 30%, negative ANA decreases proportion to 7%.2

ANA tests repeated within a one year period will be cancelled and the prior

prior result given.

When to order ENA and/or anti-dsDNA:

  • Positive ANA and features of a CTD associated with these antibodies (see adjacent table).
  • Negative ANA and
  • To look for anti-Ro/SSA*in the setting of neonatal lupus/congenital heart block, or Sjogren’s syndrome.
  • To look for anti-Jo* in the setting of myositis/interstitial lung disease.
  • ENA does not need to be repeated unless the clinical presentation changes.
  • Anti-dsDNA is sometimes repeated to follow SLE nephritis disease activity every 3-12 months.

*These antibodies are sometimes missed on ANA tests but detected in the ENA test.

ENA and anti-dsDNA will only be processed in the same order as ANA, if ANA is positive.

Connective tissue disease associations according to ENA specificity3

Typical associations
Anti-Ro/SSA / Sjogren’s, SLE, neonatal lupus
Anti-La/SSB / Sjogren’s, SLE, neonatal lupus
Anti-Sm/RNP / MCTD, SLE
Anti-Scl-70 / Systemic sclerosis
Anti-Jo / Myositis (anti-synthetase syndrome)
Anti-Sm / SLE, lupus nephritis
Anti-dsDNA / SLE, lupus nephritis
Anti-centromere* / Systemic sclerosis
Nuclear dense fine speckled pattern*4 / Healthy persons

*Specific patterns seen on an ANA test, a separate ENA test is not required.

ENA tests not listed in the table above may still be requested and will be sent to laboratories outside of VCH.

ANA: Antinuclear antibody; ENA: Extractable nuclear antigen antibody; anti-dsDNA: anti-double stranded DNA antibody; SLE: Systemic lupus erythematosus; CTD: Connective tissue disease; MCTD: Mixed connective tissue disease; VCH: Vancouver Coastal Health

References:

1. Tan EM, Feltkamp TE, Smolen JS, et al (1997) Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum40(9):1601–1611

2. Solomon DH, Kavanaugh AJ, Schur PH (2002) Evidence-based guidelines for the use of immunologic tests: antinuclear antibodytesting. Arthritis Rheum 47(4):434–444

3. Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA (2000) Guidelines for clinical use of the antinuclear antibodytest and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med 124(1):71–81

4. Mariz HA, Sato EI, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LEC (2011) Pattern on the antinuclear antibody–HEp-2test is a critical parameter for discriminating antinuclear antibody–positive healthy individuals and patients with autoimmunerheumatic diseases. Arthritis & Rheumatism 63(1):191–200